Work

The M Phase Kinase Greatwall (Gwl) Promotes Inactivation of PP2A/B55δ, a Phosphatase Directed Against CDK Phosphosites

Year: 2009

Type: article

Abstract: We have previously shown that Greatwall kinase (Gwl) is required for M phase entry and maintenance in Xenopus egg extracts. Here, we demonstrate that Gwl plays a crucial role in a novel biochemical pathway that inactivates, specifically during M phase, "antimitotic" phosphatases directed against phosphorylations catalyzed by cyclin-dependent kinases (CDKs). A major component of this phosphatase activity is heterotrimeric PP2A containing the B55delta regulatory subunit. Gwl is activated during M phase by Cdk1/cyclin B (MPF), but once activated, Gwl promotes PP2A/B55delta inhibition with no further requirement for MPF. In the absence of Gwl, PP2A/B55delta remains active even when MPF levels are high. The removal of PP2A/B55delta corrects the inability of Gwl-depleted extracts to enter M phase. These findings support the hypothesis that M phase requires not only high levels of MPF function, but also the suppression, through a Gwl-dependent mechanism, of phosphatase(s) that would otherwise remove MPF-driven phosphorylations.

Source: Molecular Biology of the Cell

DOI: 10.1091/mbc.e09-07-0643

Authors: Priscila V. Castilho, Byron C. Williams, Satoru Mochida, Yong Zhao, Michael L. Goldberg

Institutions: Cornell University, Cancer Research UK

Language: English

Topic: Microtubule and mitosis dynamics

Subfield: Cell Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

Open Access status: green

Funders: National Institutes of Health, Japan Society for the Promotion of Science, National Institute of General Medical Sciences

Award: Greatwall Kinase and the Mitotic Control of Phosphatase Activity